# MULTIPLE RESISTANCE TO ANTIBIOTICS

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 1988 · $233,854

## Abstract

Antibiotic resistance in microorganisms is now worldwide, in large
part related to the spread of plasmids and acquisition of
transposable resistances.  Among many bacteria, however, newly
discovered resistance determinants on the chromosome have
emerged, generally to one, but occasionally to more than one
group of antibiotics.  We have recently described in E. coli a
chromsomally-mediated amplifiable high-level resistance to six
structurally different antibiotics with different target sites in
mutants selected by growth in one drug.  Several genes are
involved in this "multiple antibiotic resistance" (Mar) system;
however, inactivation of one genetic locus, designated marA,
results in complete loss of all resistances.  The finding of cryptic
chromosmal genes which express resistance and which have
appeared and may emerge under clinical situations is of concern,
particularly since we already know that the resistance
mechanisms are at least in some cases distinct from those found
on plasmids.

Our proposed studies are aimed at understanding this new genetic
system and these new mechanisms of resistance before they
emerge as clinical problems.  In addition, the bacterial Mar
system has several striking characteristics in common with the
amplifiable, multiresistance found in parasites and human and
mammalian cancer cells in response to treatment with single
chemotherapeutic drugs.  Research on Mar may help to illuminate
this general biologic response of cells to growth inhibitory agents.

We shall use biochemical, molecular and genetic studies to
examine the genes, gene products, and mechanisms for the
multiple resistance phenotypes seen in the Mar mutants of E. coli.
Such studies will involve 1) mapping and cloning the genes
involved, 2) determining the genetic basis of the stepwise
selection leading to high level resistance, 3) sequencing the marA
locus, 4) sequencing some of the other genes involved in
resistance, and 5) determining gene products and the biochemical
and functional bases of the resistances.  In order to gain insight
into possible evolutionary links, we shall compare Mar-related
chromosomal to resistance to those which we have already
characterized on plasmids.

## Key facts

- **NIH application ID:** 3126817
- **Project number:** 2R01AI016756-06A4
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **SAM.gov UEI:** C1F5LNUF7W86
- **Principal Investigator:** STUART B. LEVY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $233,854
- **Award type:** 2
- **Project period:** 1980-09-30 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126817

## Citation

> US National Institutes of Health, RePORTER application 3126817, MULTIPLE RESISTANCE TO ANTIBIOTICS (2R01AI016756-06A4). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126817. Licensed CC0.

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